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glibenclamide in metformin failure type 2 diabetes patients
Poster Session 2
s344
Met monotherapy. Inadequate glycaemic control was defined as a fasting plasma glucose (FPG) concentration ?7 mmohl. Methods: Randomised four-month phase III controlled, parallel, doubleblind, double-dummy study of two dose ratio of a M/G fixed combination versus Met alone and versus Gli alone, 490 type 2 Met failure patients were enrolled, 411 of whom were randomised to one of four groups: Met 500 mg, GIi 5 mg, M /G 500 mg/2.5 mg, M/G 500 mg/5 mg. Doses were titrated for the first month from 1 to 4 tablets a day according to self glucose monitoring. Results: At end of study (4 months or last prior visit), responder rates were significantly higher in the two M/G groups compared with those observed with either Gli or Met monotherapy, either with a limit of 7% or with the healthy laboratory normal limit value of 5.6%. The mean final dose was lower in the M/G groups compared to the individual component groups. HbAlc responder I&S at 4 Months or Final Visit HbAle normality
Met
Gli
(ITT population)
5&g (N=104)
5mg (N=103)
< 7% at baseline < 7% at end point
29.8% 37.6%
30.1% 41.9%
< 5.8% at baseline
4.3% 7.5%
7.5% 11.8% 13.4
< 5.8% at end point Final dose (mg)
1660
MeUGli 5comgnsmg (N=lOl)
MetXjli
P
SoOmg/5mg (N=103)
33.3% 75.5% 7.2%
39.8% 63.8% 7.4%
0.39 0.001 0.82
14.4% 1225/6.125
25.5% 1170111.7
0.001
Conclusions: Treatment with M/G achieved statistically significant higher response rates compared with monotherapies after 4 months of treatment in patients with inadequate glycaemic control on at least submaximal dosage of Met monotherapy.
Pm8 Efficacy of a Fixed Combination MetformWGlibenclamide in Metformin Failure ‘Qpe 2 Diabetes Patients Th. ALLAVOINE, M. Marre Lyon; Bichar Hospital, Paris, France Objective: The primary objective of this study was the efficacy on HbAi, of two fixed combination metformin/glibenclamide (M/G) tablet dosages compared with metformin (Met) monotherapy and glibenclamide (Gli) monotherapy. Patients had inadequate glycaemic control while taking at least 1500 mg daily Met monotherapy. Inadequate glycaemic control was defined as a fasting plasma glucose (FPG) concentration ? 7 mmol/l. Methods: Randomised four month phase III controlled, parallel, doubleblind, double-dummy study. 490 type 2 Met failure patients were enrolled, 411 of whom were randomised to one of four groups: Met 500 mg, Gli 5 mg, M/G 500 mgQ.5 mg, M/G 500 mg/5 mg. Doses were titrated for the first month from 1 to 4 tablets a day according to a self glucose monitoring. Results: At end visit (4 months or last prior visit), HbA,, levels were significantly lower for patients in both M/G groups compared with those observed with either Gli or Met. Clinically and statistically significant differences were also observed with FPG and fructosamine. MeanHbA,,
Levels at 4 Months or Final Visit (SD. standard deviation)
HbAlc (ITT population)
Met 500mg (N=104)
Gli 5mg (N=103)
MetJGli 500mg/2.5mg (N=lOl)
Met/Gli 5M)mg/5mg (N=l03)
p
BASELINE MEAN’ (%)
7.95 zt 1.59
7.85 f
1.65
7.89 + 1.62
7.66 i
1.60
0.56
END POINT’ (%) Mean diff. (S) Changeibaseline
7.76 + 1.67 -0.19 -2.39%
7.52 + 1.74
6.75 i 1.19 -0.91 -11.88%
0.001 0.001
1660
13.4
6.69 i 1.08 -1.20 -15.21% 122516.125
Final dose (mg)
-0.33 -4.20%
1170/11.7
‘*SD
Conclusions: Treatment with M/G achieved statistically significant improvement in all parameters of glycaemic control assessed, including HbA,,, FPG, and fructosamine, compared with continued Met monother-
apy or switching to Gli monotherapy in patients with inadequate glycaemic control on at least sub maximal dosage of Met monotherapy.
P1369 Periodontal Disease and Dental Caries in Ethiopian Diabetic Patients, Tikur Anbessa Hospital (TAH), Addis Ababa, Ethiopia YEWEYENHAREG FELEKE’, Mekonen Newayz, Mengistu Alemayehu ’ ’ Department of Internal Medicine, Faculty of Medicine, Addis Ababa UniversiryAddis Ababa, Ethiopia. PO.Box 2380; ’ Mikias Dental Clinic, Addis Ababa. Ethiopia This was a cross sectional study conducted to asses the prevalence of dental and periodontal problems in diabetic patients, and to asses the relation between dental and periodontal problems to the duration of diabetes, degree of control, type of diabetes, and oral health practices. Every third patients were selected by random sampling technique from the registration book among patients coming for the regular follow up during the study period at the diabetic referral clinic of TAH. A physician recorded details of information in the questionnaire, examination of the oral cavity was conducted by dentist. General hygienic condition, plaque score, periodontal indices, gingivitis score, degree of mobility, gingival recession, probing depth, severity of bone loss and dental caries were defined according to the standard definition. A total of 649 diabetic patients were involved in the study among these 309 (47.6%) were males, 340 (52.4%) were females, 324(49.9%) were Type1 and 325 (50.1%) were Type 2 diabetes mellitus. The mean f SD age was 42.0f 15.6 yrs, the mean duration of diabetes was 10.2 f 6.6 years, 518 (79.6%) patients were on insulin, 121 (18.6%) were on oral agent and 12 were on diet. The prevalence of dental caries was 23% and gingivitis 96.5%. plaque 96.52, gingival recession in 94.8% abnormal mobility in 19%, bone loss in 62.1%. 20.5% of patients lost incisors, 5.9% canine, 17.0% premolar, 56.6% molar teeth. The mean duration of diabetes was significantly associated with general hygienic condition of the oral cavity, gingival recession, probing depth, severity of bone loss (p=O.Ol, p=0.0009, p=O.O002, p = 0.02 respectively). There was no significant association between the mean fasting blood sugar and periodontal disease and dental caries (PzO.05). There was significant association between the type of diabetes and periodontal disease (Pt0.05). There was significant association between the use of tooth brush and general hygienic condition of the teeth, plaque formation (p=O.Ol, p=O.28 respectively), but no significant association with gingivitis, probing depth, severity of bone loss and dental caries (p.O.05). In conclusion periodontal diseases are sever and more common in diabetes. We recommended strengthening the health education about the oral health care practice and organizing an effective preventive and management dental service for diabetes.
P1370 A New Anti-Diabetic Compound, CLX-0921: Efficacy in Rodent Models of ‘Qpe II Diabetes and Syndrome X BISWAJIT NAG, Satya Medicherla, Maya S. Gowri, Deben Dey, Partha Neogi, Gerald M. Reaven’.Calyx Therapeutics Inc., Hayward, CA 94545; ’ Stanford UniversitySchool of Medicine, Stanford, CA 94305, USA CLX-0921 is a new synthetic anti-diabetic compound containing a natural product-derived analog linked to a thiazolidinedione ring (MW 520). When given orally at a dose of 5-10 mg/kg body weight, CLX-0921 lowered blood glucose levels (5060%) in ob/ob and db/db diabetic mjce along with remarkable reduction in serum insulin, triglycerides and free fatty acid levels. In Zucker (fa/fa) and Zucker diabetic fatty (ZDF) rats, oral treatment with CLX-0921 showed similar effects. In contrast, CLX-0921 did not lower blood glucose levels in normal rats, STZ-induced diabetic rats, or NOD mice. Unlike some of the known TZD molecules, treatment with CLX-0921 did not cause cardiac hypertrophy or a decrease
s344
Met monotherapy. Inadequate glycaemic control was defined as a fasting plasma glucose (FPG) concentration ?7 mmohl. Methods: Randomised four-month phase III controlled, parallel, doubleblind, double-dummy study of two dose ratio of a M/G fixed combination versus Met alone and versus Gli alone, 490 type 2 Met failure patients were enrolled, 411 of whom were randomised to one of four groups: Met 500 mg, GIi 5 mg, M /G 500 mg/2.5 mg, M/G 500 mg/5 mg. Doses were titrated for the first month from 1 to 4 tablets a day according to self glucose monitoring. Results: At end of study (4 months or last prior visit), responder rates were significantly higher in the two M/G groups compared with those observed with either Gli or Met monotherapy, either with a limit of 7% or with the healthy laboratory normal limit value of 5.6%. The mean final dose was lower in the M/G groups compared to the individual component groups. HbAlc responder I&S at 4 Months or Final Visit HbAle normality
Met
Gli
(ITT population)
5&g (N=104)
5mg (N=103)
< 7% at baseline < 7% at end point
29.8% 37.6%
30.1% 41.9%
< 5.8% at baseline
4.3% 7.5%
7.5% 11.8% 13.4
< 5.8% at end point Final dose (mg)
1660
MeUGli 5comgnsmg (N=lOl)
MetXjli
P
SoOmg/5mg (N=103)
33.3% 75.5% 7.2%
39.8% 63.8% 7.4%
0.39 0.001 0.82
14.4% 1225/6.125
25.5% 1170111.7
0.001
Conclusions: Treatment with M/G achieved statistically significant higher response rates compared with monotherapies after 4 months of treatment in patients with inadequate glycaemic control on at least submaximal dosage of Met monotherapy.
Pm8 Efficacy of a Fixed Combination MetformWGlibenclamide in Metformin Failure ‘Qpe 2 Diabetes Patients Th. ALLAVOINE, M. Marre Lyon; Bichar Hospital, Paris, France Objective: The primary objective of this study was the efficacy on HbAi, of two fixed combination metformin/glibenclamide (M/G) tablet dosages compared with metformin (Met) monotherapy and glibenclamide (Gli) monotherapy. Patients had inadequate glycaemic control while taking at least 1500 mg daily Met monotherapy. Inadequate glycaemic control was defined as a fasting plasma glucose (FPG) concentration ? 7 mmol/l. Methods: Randomised four month phase III controlled, parallel, doubleblind, double-dummy study. 490 type 2 Met failure patients were enrolled, 411 of whom were randomised to one of four groups: Met 500 mg, Gli 5 mg, M/G 500 mgQ.5 mg, M/G 500 mg/5 mg. Doses were titrated for the first month from 1 to 4 tablets a day according to a self glucose monitoring. Results: At end visit (4 months or last prior visit), HbA,, levels were significantly lower for patients in both M/G groups compared with those observed with either Gli or Met. Clinically and statistically significant differences were also observed with FPG and fructosamine. MeanHbA,,
Levels at 4 Months or Final Visit (SD. standard deviation)
HbAlc (ITT population)
Met 500mg (N=104)
Gli 5mg (N=103)
MetJGli 500mg/2.5mg (N=lOl)
Met/Gli 5M)mg/5mg (N=l03)
p
BASELINE MEAN’ (%)
7.95 zt 1.59
7.85 f
1.65
7.89 + 1.62
7.66 i
1.60
0.56
END POINT’ (%) Mean diff. (S) Changeibaseline
7.76 + 1.67 -0.19 -2.39%
7.52 + 1.74
6.75 i 1.19 -0.91 -11.88%
0.001 0.001
1660
13.4
6.69 i 1.08 -1.20 -15.21% 122516.125
Final dose (mg)
-0.33 -4.20%
1170/11.7
‘*SD
Conclusions: Treatment with M/G achieved statistically significant improvement in all parameters of glycaemic control assessed, including HbA,,, FPG, and fructosamine, compared with continued Met monother-
apy or switching to Gli monotherapy in patients with inadequate glycaemic control on at least sub maximal dosage of Met monotherapy.
P1369 Periodontal Disease and Dental Caries in Ethiopian Diabetic Patients, Tikur Anbessa Hospital (TAH), Addis Ababa, Ethiopia YEWEYENHAREG FELEKE’, Mekonen Newayz, Mengistu Alemayehu ’ ’ Department of Internal Medicine, Faculty of Medicine, Addis Ababa UniversiryAddis Ababa, Ethiopia. PO.Box 2380; ’ Mikias Dental Clinic, Addis Ababa. Ethiopia This was a cross sectional study conducted to asses the prevalence of dental and periodontal problems in diabetic patients, and to asses the relation between dental and periodontal problems to the duration of diabetes, degree of control, type of diabetes, and oral health practices. Every third patients were selected by random sampling technique from the registration book among patients coming for the regular follow up during the study period at the diabetic referral clinic of TAH. A physician recorded details of information in the questionnaire, examination of the oral cavity was conducted by dentist. General hygienic condition, plaque score, periodontal indices, gingivitis score, degree of mobility, gingival recession, probing depth, severity of bone loss and dental caries were defined according to the standard definition. A total of 649 diabetic patients were involved in the study among these 309 (47.6%) were males, 340 (52.4%) were females, 324(49.9%) were Type1 and 325 (50.1%) were Type 2 diabetes mellitus. The mean f SD age was 42.0f 15.6 yrs, the mean duration of diabetes was 10.2 f 6.6 years, 518 (79.6%) patients were on insulin, 121 (18.6%) were on oral agent and 12 were on diet. The prevalence of dental caries was 23% and gingivitis 96.5%. plaque 96.52, gingival recession in 94.8% abnormal mobility in 19%, bone loss in 62.1%. 20.5% of patients lost incisors, 5.9% canine, 17.0% premolar, 56.6% molar teeth. The mean duration of diabetes was significantly associated with general hygienic condition of the oral cavity, gingival recession, probing depth, severity of bone loss (p=O.Ol, p=0.0009, p=O.O002, p = 0.02 respectively). There was no significant association between the mean fasting blood sugar and periodontal disease and dental caries (PzO.05). There was significant association between the type of diabetes and periodontal disease (Pt0.05). There was significant association between the use of tooth brush and general hygienic condition of the teeth, plaque formation (p=O.Ol, p=O.28 respectively), but no significant association with gingivitis, probing depth, severity of bone loss and dental caries (p.O.05). In conclusion periodontal diseases are sever and more common in diabetes. We recommended strengthening the health education about the oral health care practice and organizing an effective preventive and management dental service for diabetes.
P1370 A New Anti-Diabetic Compound, CLX-0921: Efficacy in Rodent Models of ‘Qpe II Diabetes and Syndrome X BISWAJIT NAG, Satya Medicherla, Maya S. Gowri, Deben Dey, Partha Neogi, Gerald M. Reaven’.Calyx Therapeutics Inc., Hayward, CA 94545; ’ Stanford UniversitySchool of Medicine, Stanford, CA 94305, USA CLX-0921 is a new synthetic anti-diabetic compound containing a natural product-derived analog linked to a thiazolidinedione ring (MW 520). When given orally at a dose of 5-10 mg/kg body weight, CLX-0921 lowered blood glucose levels (5060%) in ob/ob and db/db diabetic mjce along with remarkable reduction in serum insulin, triglycerides and free fatty acid levels. In Zucker (fa/fa) and Zucker diabetic fatty (ZDF) rats, oral treatment with CLX-0921 showed similar effects. In contrast, CLX-0921 did not lower blood glucose levels in normal rats, STZ-induced diabetic rats, or NOD mice. Unlike some of the known TZD molecules, treatment with CLX-0921 did not cause cardiac hypertrophy or a decrease